{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:37:46Z","timestamp":1790937466065,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,8,31]],"date-time":"2011-08-31T00:00:00Z","timestamp":1314748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Urokinase plasminogen activator (uPA), uPA receptor (uPAR), and PA inhibitor 1 (PAI\u20101) have pivotal roles in the proliferation and invasion of several cell types, including synovial fibroblasts (SFs). The aim of this study was to investigate the possibility of controlling the invasion of rheumatoid arthritis (RA) SFs in vitro and in vivo by inhibiting uPA and uPAR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Normal SFs, SFs from patients with RA, and SFs from patients with psoriatic arthritis (PsA) were used. The levels of uPA, uPAR, and PAI\u20101 were measured by enzyme\u2010linked immunosorbent assay and reverse transcription\u2013polymerase chain reaction analysis of messenger RNA. The activity of uPA was studied by zymography. Proliferation was measured by cell counting, and cell invasion was measured with a Boyden chamber assembled with Matrigel\u2010coated porous filters. Human cartilage and RA SF implantation in the SCID mouse model of RA were used to study cartilage invasion in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RA SFs and PsA SFs overexpressed uPAR and as a result were more active than their normal counterparts in terms of both Matrigel invasion and proliferation. This effect was counteracted by a specific inhibitor of uPA enzymatic activity (WX\u2010340) and by uPAR antisense treatment. The use of both WX\u2010340 and uPAR antisense treatment in vitro showed cooperative effects in RA SFs that were more intense than the effects of either treatment alone. Significant inhibition of cartilage invasion was obtained in vivo with uPAR antisense treatment, while uPA inhibition was inefficient, either alone or in combination with antisense treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The decrease in uPAR expression in RA SFs reduced invasion of human cartilage in vitro and in the SCID mouse model.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30439","type":"journal-article","created":{"date-parts":[[2011,5,5]],"date-time":"2011-05-05T15:54:29Z","timestamp":1304610869000},"page":"2584-2594","source":"Crossref","is-referenced-by-count":30,"title":["Reduction of in vitro invasion and in vivo cartilage degradation in a SCID mouse model by loss of function of the fibrinolytic system of rheumatoid arthritis synovial fibroblasts"],"prefix":"10.1002","volume":"63","author":[{"given":"Simona","family":"Serrat\u00ec","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Margheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Chill\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"M\u00fcller\u2010Ladner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Benucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Fibbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Del Rosso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,8,31]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"485","article-title":"The urokinase\u2010type plasminogen activator system and inflammatory joint diseases","volume":"17","author":"Del Rosso M","year":"1999","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20306"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000209518.58252.17"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015531321445"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH05-01-0054"},{"key":"e_1_2_6_7_2","first-page":"139","article-title":"Interstitial collagenase (matrix metalloproteinase 1) associated with the plasma membrane of both neoplastic and nonneoplastic cells","volume":"11","author":"Whitelock JM","year":"1991","journal-title":"Invasion Metastasis"},{"key":"e_1_2_6_8_2","first-page":"364","article-title":"Rheumatoid synovial fibroblasts constitutively express the fibrinolytic pattern of invasive tumor\u2010like cells","volume":"23","author":"Guiducci S","year":"2005","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2008.06582.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10498"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62285-7"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/35.5.416"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(98)00293-8"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.9.550"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00608-3"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62299-7"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar606"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(88)90277-7"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.001"},{"key":"e_1_2_6_20_2","first-page":"340","article-title":"Antisense targeting of the urokinase receptor blocks urokinase\u2010dependent proliferation, chemoinvasion, and chemotaxis of human synovial cells and chondrocytes in vitro","volume":"110","author":"Fibbi G","year":"1998","journal-title":"Proc Assoc Am Phys"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21972"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2309"},{"key":"e_1_2_6_24_2","first-page":"109","article-title":"Molecular basis of specific inhibition of urokinase plasminogen activator by amiloride","volume":"17","author":"Jankun J","year":"1999","journal-title":"Cancer Biochem Biophys"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90782-8"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20562"},{"key":"e_1_2_6_27_2","first-page":"90","article-title":"Reversion of the invasive phenotype of transformed human fibroblasts by anti\u2010messenger oligonucleotide inhibition of urokinase receptor gene expression","volume":"55","author":"Quattrone A","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302456"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.10.036"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.3109\/s101650170027"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2050"},{"key":"e_1_2_6_32_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.4049\/jimmunol.126.3.851","article-title":"Stimulation of human synovial fibroblast plasminogen activator production by mononuclear cell supernatants","volume":"126","author":"Hamilton JA","year":"1981","journal-title":"J Immunol"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V77.4.841.841"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310817"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.3.151"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.30439","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.30439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T12:42:20Z","timestamp":1697028140000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.30439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8,31]]},"references-count":34,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1002\/art.30439"],"URL":"https:\/\/doi.org\/10.1002\/art.30439","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,8,31]]}}}